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Oncol Lett. 2013 Dec;6(6):1641-1645. Epub 2013 Oct 9.

Prognostic impact of p16 and p21 on gastroenteropancreatic neuroendocrine tumors.

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Department of Epidemiology, College of Public Health of Zhengzhou University, Zhengzhou, Henan 450001, P.R. China ; Henan Cancer Research and Control Office, Henan Cancer Hospital, Zhengzhou, Henan 450008, P.R. China.


Aberrant expression of the cell cycle kinase inhibitors, p16 and p21, has been associated with poor prognosis in a number of human malignancies. These proteins may also be involved in the development and progression of gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The present study aimed to investigate protein levels of p16 and p21 in GEP-NETs and to evaluate their clinical significance. p16 and p21 protein expression was tested immunohistochemically in the tissue samples of 68 GEP-NETs. The association between expression and clinicopathological characteristics and overall survival was assessed. Low expression of p16 (no positive nuclear staining) was found in 37 (54%) cases and high p21 expression (≥5% positive nuclear staining) was detected in 23 (34%) cases. Low p16 protein levels indicated a poorer prognosis for patients graded as G2 subgroup in the univariate analysis (relative risk, 4.4; 95% CI, 1.8-10.6). No significant correlation was found between the expression of p21 and any of the clinicopathological variables. The present study indicates a prognostic relevance for p16 immunoreactivity. Low levels of p16 protein were associated with a shorter survival in the G2 subgroup of GEP-NETs. p21 protein expression was not identified to be useful as a predictive indicator in GEP-NETs.


gastroenteropancreatic neuroendocrine tumor; immunohistochemistry; p16; p21

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